Individuals with Familial Adenomatous Polyposis (FAP) harbor a germline mutation in APC. The major clinical manifestation is development of multiple colonic tumors at a young age due to stochastic loss of the remaining APC allele. Extra-colonic features may occur, including periampullary tumors, gastric abnormalities, and congenital hypertrophy of the retinal pigment epithelium (CHRPE). The objective of this study was to develop a mouse model that simulates these features of FAP. To accomplish this, we combined our Lrig1-CreERT2/+ mice with Apcfl/+ mice, eliminated one copy of Apc in Lrig1+ progenitor cells with tamoxifen injection and monitored tumor formation in the colon by colonoscopy and positron emission tomography (PET). Initial loss of one Apc allele in Lrig1+ cells results in a predictable pattern of preneoplastic changes, culminating in multiple distal colonic tumors within 50 days of induction, as well as the extra-colonic manifestations of FAP mentioned above. We show that tumor formation can be monitored by noninvasive PET imaging. This inducible stem cell-driven model recapitulates features of FAP and offers a tractable platform to monitor therapeutic interventions over time by colonoscopy and non-invasive imaging.
- Stem Cells
- Colorectal Cancer
- Mouse Models
- Copyright © 2013, American Journal of Physiology- Gastrointestinal and Liver Physiology